The Role of Interferons in Long Covid Infection

Abstract:

Although the new generation of vaccines and anti-COVID-19 treatment regimens facilitated the management of acute COVID-19 infections, concerns about post-COVID-19 syndrome or Long Covid are rising. This issue can increase the incidence and morbidity of diseases such as diabetes, and cardiovascular, and lung infections, especially among patients suffering from neurodegenerative disease, cardiac arrhythmias, and ischemia.

There are numerous risk factors that cause COVID-19 patients to experience post-COVID-19 syndrome. Three potential causes attributed to this disorder include immune dysregulation, viral persistence, and autoimmunity. Interferons (IFNs) are crucial in all aspects of post-COVID-19 syndrome etiology.

In this review, we discuss the critical and double-edged role of IFNs in post-COVID-19 syndrome and how innovative biomedical approaches that target IFNs can reduce the occurrence of Long Covid infection.

Source: Karbalaeimahdi M, Farajnia S, Bargahi N, Ghadiri-Moghaddam F, Rasouli Jazi HR, Bakhtiari N, Ghasemali S, Zarghami N. The Role of Interferons in Long Covid Infection. J Interferon Cytokine Res. 2023 Feb;43(2):65-76. doi: 10.1089/jir.2022.0193. PMID: 36795973. https://pubmed.ncbi.nlm.nih.gov/36795973/

Association of Post-COVID-19 Condition Symptoms and Employment Status

Abstract:

Importance: Little is known about the functional correlates of post-COVID-19 condition (PCC), also known as long COVID, particularly the relevance of neurocognitive symptoms.

Objective: To characterize prevalence of unemployment among individuals who did, or did not, develop PCC after acute infection.

Design, setting, and participants: This survey study used data from 8 waves of a 50-state US nonprobability internet population-based survey of respondents aged 18 to 69 years conducted between February 2021 and July 2022.

Main outcomes and measures: The primary outcomes were self-reported current employment status and the presence of PCC, defined as report of continued symptoms at least 2 months beyond initial month of symptoms confirmed by a positive COVID-19 test.

Results: The cohort included 15 308 survey respondents with test-confirmed COVID-19 at least 2 months prior, of whom 2236 (14.6%) reported PCC symptoms, including 1027 of 2236 (45.9%) reporting either brain fog or impaired memory. The mean (SD) age was 38.8 (13.5) years; 9679 respondents (63.2%) identified as women and 10 720 (70.0%) were White. Overall, 1418 of 15 308 respondents (9.3%) reported being unemployed, including 276 of 2236 (12.3%) of those with PCC and 1142 of 13 071 (8.7%) of those without PCC; 8229 respondents (53.8%) worked full-time, including 1017 (45.5%) of those with PCC and 7212 (55.2%) without PCC. In survey-weighted regression models excluding retired respondents, the presence of PCC was associated with a lower likelihood of working full-time (odds ratio [OR], 0.71 [95% CI, 0.63-0.80]; adjusted OR, 0.84 [95% CI, 0.74-0.96]) and with a higher likelihood of being unemployed (OR, 1.45 [95% CI, 1.22-1.73]; adjusted OR, 1.23 [95% CI, 1.02-1.48]). The presence of any cognitive symptom was associated with lower likelihood of working full time (OR, 0.70 [95% CI, 0.56-0.88]; adjusted OR, 0.75 [95% CI, 0.59-0.84]).

Conclusions and relevance: PCC was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. The presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to treat and manage PCC symptoms.

Source: Perlis RH, Lunz Trujillo K, Safarpour A, Santillana M, Ognyanova K, Druckman J, Lazer D. Association of Post-COVID-19 Condition Symptoms and Employment Status. JAMA Netw Open. 2023 Feb 1;6(2):e2256152. doi: 10.1001/jamanetworkopen.2022.56152. PMID: 36790806; PMCID: PMC9932847. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932847/(Full text)

Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study

Abstract:

Objective: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition.

Study design: This was a cross-sectional questionnaire-based survey.

Methods: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses.

Results: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (β = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (β = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (β = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (β = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (β = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (β = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (β = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (β = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (β = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (β = -0.51, 95% CI = -0.94 to -0.09).

Conclusions: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.

Source: Morioka S, Tsuzuki S, Maruki T, Terada M, Miyazato Y, Kutsuna S, Saito S, Shimanishi Y, Takahashi K, Sanada M, Ashida S, Akashi M, Kuge C, Osanai Y, Tanaka K, Suzuki M, Hayakawa K, Ohmagari N. Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study. Public Health. 2023 Feb 13;216:39-44. doi: 10.1016/j.puhe.2023.01.008. Epub ahead of print. PMID: 36791649. https://www.sciencedirect.com/science/article/pii/S0033350623000173?via%3Dihub (Full text)

Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study

Abstract:

Symptoms of long COVID-19 syndrome (long COVID-19) are reported by 80% of convalescents up to several months after contracting the coronavirus-19 disease (COVID-19). The study aimed to assess the frequency and correlations of long COVID symptoms with sex, disease severity, time since the onset of the disease, and exercise capacity in a population of Polish convalescents hospitalized as a part of a rehabilitation program after COVID-19.

The retrospective analysis was carried out based on medical records concerning reported symptoms, comorbidities, exercise capacity, fatigue and dyspnea on Borg’s scale, arterial oxygen saturation (SpO2), spirometric parameters, chest X-rays/computed tomography scans, systolic pulmonary artery pressure, and left ventricular ejection fraction. The study involved 471 patients aged 63.83 ± 9.93 years who had been hospitalized 191.32 ± 75.69 days from the onset of COVID-19, of which 269 (57.1%) were women. The most common symptoms were fatigue (99.57%), dyspnea (99.36%), and myalgia (97.03%). Women reported more symptoms than men (p < 0.001) and rated their fatigue as more severe (p = 0.021). Patients with depressed moods reported more physical symptoms than others (p < 0.001).

Most long COVID symptoms, including dyspnea, fatigue, and depressive symptoms, were found with the same frequency in patients 12-24 weeks and >24 weeks after recovery (p = 0.874, p = 0.400, and p = 0.320, respectively), regardless of acute COVID-19 severity (p = 0.240, p = 0.826, and p = 0.108, respectively). Dyspnea severity correlated with forced vital capacity (FVC) (r = -0.153, p = 0.005), and forced expiratory volume in one second (FEV1) (r = -0.142, p = 0.008). Fatigue severity correlated with impaired FVC and FEV1 (both r = -0.162, p = 0.003). Fatigue and dyspnea inversely correlated with the distance in a six-minute walk test (r = -0.497, p < 0.001, and r = -0.327, p < 0.001).

In conclusion, in our cohort, long COVID symptoms are more common in women. Dyspnea/fatigue and depressive symptoms do not tend to subside after an average six-month recovery period. The intensity of perceived fatigue may be exaggerated by the coexistence of neuropsychiatric disorders. Increased fatigue and dyspnea correlate with impaired spirometric parameters and significantly affects convalescents’ exercise capacity.

Source: Paradowska-Nowakowska E, Łoboda D, Gołba KS, Sarecka-Hujar B. Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study. Life (Basel). 2023 Feb 11;13(2):508. doi: 10.3390/life13020508. PMID: 36836865; PMCID: PMC9961608. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961608/ (Full text)

Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19

Abstract:

Background: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology.

Method: Data from four releases of the Census Bureau’s Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results.

Results: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451).

Conclusions: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.

Source: Jacobs MM, Evans E, Ellis C. Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19. J Natl Med Assoc. 2023 Feb 13:S0027-9684(23)00025-1. doi: 10.1016/j.jnma.2023.01.016. Epub ahead of print. PMID: 36792456; PMCID: PMC9923441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923441/ (Full text)

Assessment of short- and long-term functionality and quality of life in patients with post-acute COVID-19 syndrome

Abstract:

Background: Although the number of new cases of coronavirus 2019 (COVID-19) has been drastically reduced worldwide, patients who demonstrate long-term symptoms need more attention from health systems, as these symptoms can negatively affect functionality and quality of life.

Objective: To evaluate muscle function and quality of life at 3, 6, 9 and 12 months in patients with post-acute COVID-19 syndrome and to assess their associations with general fatigue and lung function.

Methods: This observational and longitudinal study evaluated patients with post-acute COVID-19 syndrome. Participants were subjected to the following evaluations: Short Form-36; handgrip strength; Functional Assessment of Chronic Illness Therapy-Fatigue scale; and spirometry.

Results: Among the 350 participants who were evaluated in the third month, 74.6%, 61.4% and 45.4% reported general fatigue, dyspnoea and cough, respectively. In the comparisons between the third month and the sixth month, there were significant increases in Functional Assessment of Chronic Illness Therapy-Fatigue scale, pulmonary function and several Short Form-36 domains. In the comparisons between the sixth month and the ninth month, there was a significant increase only in the social functioning domain of the Short Form-36. In the comparisons between the ninth month and the twelfth month, there was an increase only in some Short Form-36 domains. Significant correlations were observed between the Short Form-36 domains with Functional Assessment of Chronic Illness Therapy-Fatigue scale, handgrip strength and pulmonary function.

Conclusion: In patients with post-acute COVID-19 syndrome, there was a progressive improvement in quality of life, general fatigue and pulmonary function during the 12 months of follow-up, with this improvement being more pronounced in the first 6 months. There was a relationship between functionality and quality of life in these patients.

Source: de Azevedo Vieira JE, Mafort TT, Monnerat LB, da Cal MS, Ghetti ATA, Lopes AJ. Assessment of short- and long-term functionality and quality of life in patients with post-acute COVID-19 syndrome. J Back Musculoskelet Rehabil. 2023 Feb 2. doi: 10.3233/BMR-220308. Epub ahead of print. PMID: 36776041. https://content.iospress.com/articles/journal-of-back-and-musculoskeletal-rehabilitation/bmr220308 (Full text)

Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19

Abstract:

Emerging evidence shows that individuals with COVID-19 who survive the acute phase of illness may experience lingering symptoms in the following months. There is no clear indication as to whether these symptoms persist for a short time before resolving or if they persist for a long time. In this review, we will describe the symptoms that persist over time and possible predictors in the acute phase that indicate long-term persistence.
Based on the literature available to date, fatigue/weakness, dyspnea, arthromyalgia, depression, anxiety, memory loss, slowing down, difficulty concentrating and insomnia are the most commonly reported persistent long-term symptoms. The extent and persistence of these in long-term follow-up is not clear as there are still no quality studies available.
The evidence available today indicates that female subjects and those with a more severe initial disease are more likely to suffer permanent sequelae one year after the acute phase. To understand these complications, and to experiment with interventions and treatments for those at greater risk, we must first understand the physio-pathological mechanisms that sustain them.
Source: Fabbri A, Voza A, Riccardi A, Vanni S, De Iaco F on behalf of the Study & Research Center of the Italian Society of Emergency Medicine (SIMEU). Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19. Viruses. 2023; 15(2):485. https://doi.org/10.3390/v15020485 (Full text)

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review

Abstract:

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19.
The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms.
A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a.
The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood–nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.
Source: Reyes-Long S, Cortés-Altamirano JL, Bandala C, Avendaño-Ortiz K, Bonilla-Jaime H, Bueno-Nava A, Ávila-Luna A, Sánchez-Aparicio P, Clavijo-Cornejo D, Dotor-LLerena AL, Cabrera-Ruiz E, Alfaro-Rodríguez A. Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review. International Journal of Molecular Sciences. 2023; 24(4):3574. https://doi.org/10.3390/ijms24043574 https://www.mdpi.com/1422-0067/24/4/3574 (Full text)

Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected

Abstract:

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome.

A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain.

Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.

Source: Ferrara, F., Zovi, A., Masi, M. et al. Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected. Naunyn-Schmiedeberg’s Arch Pharmacol (2023). https://doi.org/10.1007/s00210-023-02417-5 https://link.springer.com/article/10.1007/s00210-023-02417-5 (Full text)

Vaccination status and long COVID symptoms in patients discharged from hospital

Abstract:

Effective vaccination against coronavirus mitigates the risk of hospitalisation and mortality; however, it is unclear whether vaccination status influences long COVID symptoms in patients who require hospitalisation. The available evidence is limited to outpatients with mild disease.

Here, we evaluated 412 patients (age: 60 ± 16 years, 65% males) consecutively admitted to two Hospitals in Brazil due to confirmed coronavirus disease 2019 (COVID-19). Compared with patients with complete vaccination (n = 185) before infection or hospitalisation, those with no or incomplete vaccination (n = 227) were younger and had a lower frequency of several comorbidities.

Data during hospitalisation revealed that the no or incomplete vaccination group required more admissions to the intensive care unit (ICU), used more corticosteroids, and had higher rates of pulmonary embolism or deep venous thrombosis than the complete vaccination group. Ninety days after hospital discharge, patients with no or incomplete vaccination presented a higher frequency of symptoms (≥ 1) than patients with complete vaccination (40 vs. 27%; p = 0.013).

After adjusting for confounders, no or incomplete vaccination (odds ratio [OR] 1.819; 95% confidence interval [CI] 1.175-2.815), female sex (OR 2.435; 95% CI 1.575-3.764) and ICU admission during hospitalisation (OR 1.697; 95% CI 1.062-2.712) were independently associated with ≥ 1 symptom 90 days after hospital discharge.

In conclusion, even in patients with severe COVID-19, vaccination mitigates the probability of long COVID symptoms.

Source: Nascimento TCDC, do Valle Costa L, Ruiz AD, Ledo CB, Fernandes VPL, Cardoso LF, Junior JMV, Saretta R, Kalil-Filho R, Drager LF. Vaccination status and long COVID symptoms in patients discharged from hospital. Sci Rep. 2023 Feb 11;13(1):2481. doi: 10.1038/s41598-023-28839-y. PMID: 36774419; PMCID: PMC9922040. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922040/ (Full text)